446262-61-9Relevant academic research and scientific papers
Spiroleptosphol isolated from Leptosphaeria doliolum
Hashimoto, Masaru,Tsushima, Taro,Murakami, Takanori,Nomiya, Masahiro,Takada, Noboru,Tanaka, Kazuaki
scheme or table, p. 4228 - 4231 (2009/04/06)
A novel γ-methylidene-spirobutanolide spirolephtoshol (1) was isolated from ascomycetous fungus Leptosphaeria doliolum as a cytotoxic compound. The relative structure was established by the NMR analysis involving the NOE experiments. Absolute structure of the bicyclic moiety was determined by chemical derivation followed by the CD analysis. The relative and absolute stereochemistry of the side chain was established by comparison of the 1H NMR spectra and the chiral GC chromatograms of the degradation product with the synthetic samples.
Approach toward the total synthesis of orevactaene. 2. Convergent and stereoselective synthesis of the C18-C31 domain of orevactaene. Evidence for the relative configuration of the side chain.
Organ, Michael G,Bilokin, Yaroslav V,Bratovanov, Svetoslav
, p. 5176 - 5183 (2007/10/03)
The synthesis of the C18-C31 subunit of orevactaene (1) in an enantioselective and convergent manner is reported. Four chiral centers in the structure (i.e., carbons 23, 25, 32, and 33) have unknown configuration; thus, a modular approach has been devised to link the two stereocenter-containing ends of the structure together via a trisubstituted olefin template to ultimately produce all possible diastereomers of the target. Keys to the success of this approach include (i) an efficient synthesis of four diastereomeric hydrophobic tails (C22-C29) of the molecule with two stereogenic centers at C23 and C25; (ii) the synthesis of three stereodefined trisubstituted olefins 37, 38, and 43 using palladium(0)-catalyzed hydrometalation and metallometalation; and (iii) the convergent assembly of the aforementioned sections by a 'one-pot' lithium/halogen exchange, boron/lithium exchange, borate ester saponification, and Suzuki cross-coupling followed by oxidative deprotection. The sequence provided the desired aldehydes 49 and 50 as single isomers in good yields. Compiled spectroscopic data from the literature and present work provides evidence that the relative configuration of the methyl groups in the side chain of orevactaene may be 1,3-syn, which will be confirmed when the total synthesis has been completed. These results have paved the way for a parallel synthesis approach to prepare all 16 possible stereoisomers of orevactaene so that the relative and absolute stereochemistry of this compound can be determined.
Total synthesis of zaragozic acid A (squalestatin S1). Degradation to a relay compound and reassembly of the natural product
Stoermer, Doris,Caron, Stephane,Heathcock, Clayton H.
, p. 9115 - 9125 (2007/10/03)
Zaragozic acid A (squalestatin S1) (1) was converted into the simpler derivative 2, which was reconverted into the natural product, thus establishing 2 as a viable relay compound for total synthesis of 1. The degradation consisted of formation of the tri-tert-butyl ester (3), from which the two side chains were sequentially removed to obtain 8. Aldehyde 8 was converted into dimethyl acetal 2 in standard fashion. The C6 acyl side chain 14 was prepared from (S)-2-methylbutanol ('active amyl alcohol'), and the desired 4S configuration was obtained by use of Evans asymmetric enolate methylation. The C1 alkyl side chain was prepared as stannane 23a from (R)-2-methyl-3-phenylpropanol (21). For conversion of 2 back into zaragozic acid A, the dimethyl acetal was first converted into the cyclic acetal 17, thus protecting the C7 hydroxyl group. The remaining hydroxyl group was then acylated with acid 14 to obtain 18, which was transformed into aldehyde 20. The C1 alkyl chain was elaborated by the addition of a chiral α-alkoxyorganocerium reagent, obtained from 23a, to aldehyde 20. The resulting mixture of diastereomeric secondary alcohols was converted into zaragozic acid A (1) in six steps.
